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In vivo, tissue-level, mechanical thresholds for axonal injury in the guinea pig optic nerve were determined by comparing morphological injury to estimated in vivo tissue strain. The right optic nerve of adult male guinea pigs was stretched to one of seven ocular displacement levels. Morphological injury was detected three days post-stretch with neurofilament immunohistochemical staining (NF68). A companion set of in situ experiments was used to determine the empirical relationship between ocular displacement and optic nerve stretch. Logistics regression analysis, combined with sensitivity and specificity measures and receiver operating characteristic (ROC) curves were then used to predict strain thresholds for axonal injury. From this analysis, we determined three Lagrangian strain- based thresholds for morphological damage to the guinea pig white matter.

A finite element model of cerebral contusion in the rat was developed and compared to experimental injury maps demonstrating blood-brain barrier (BBB) breakdown. The model was exercised at the nine unique loading conditions used experimentally. Logistic regressions of four variables, maximum principal logarithmic strain (LEP), maximum principal stress (SP), strain energy density (SEN), and von Mises stress (MIS) demonstrated highly significant confidence in the prediction of the 50th percentile values (chi-squared, p<0.00001). However, only values for LEP were invariant across loading conditions. These results suggest that the BBB is most sensitive to LEP, and that breakdown occurs above a strain of 0.188 +/- 0.0324.